tbuckley/cabot-search huggingface dataset:
Assessing PSA levels as prognostic of overall survival (OS) in men with metastatic hormone-sensitive prostate cancer (mHSPC).
Authors: Susan Halabi, Akash Roy, Siyuan S Guo, Larysa Rydzewska, Peter Godolphin, Maha H. A. Hussain, Catherine Tangen, Ian Thompson, Wanling Xie, Michael Anthony Carducci, Matthew Raymond Smith, Michael J. Morris, Gwenaelle Gravis, David P. Dearnaley, Paul Verhagen, Takayuki Goto, Jayne F. Tierney, Nicholas D. James, Marc E. Buyse, Christopher Sweeney
Journal: Journal of Clinical Oncology (2023)

5070 Background: Prior data have shown that prostate specific antigen (PSA) ≤ 0.2 ng/dL at 6-7 months with androgen deprivation therapy (ADT) with testosterone suppression (TS) alone is prognostic of OS. We hypothesized that PSA ≤0.1 ng/dL at 7 months would be a stronger prognostic for OS in men with mHSPC treated with TS alone. This hypothesis was investigated by the STOPCAP M1 collaborators. Methods: Individual patient data from 13 eligible randomized trials comparing treatment regimens (TS or TS + docetaxel in the control or research arms in mHSPC trials were utilized. Landmark survival analyses were performed at 7 months after ADT initiation. Overall survival was computed as the time from 7 months after start of initial TS to death or date of last follow for patients who started TS prior to randomization or 7 months after randomization to death or date last follow-up for patients who started TS after randomization. PSA measurements between 4-7 months after ADT were selected and cut off-points of PSA ≤0.2, 0.2-4, and &gt;4 ng/dL or PSA ≤0.1, 0.1-0.2, 0.2-4, and &gt;4 ng/dL were considered. The proportional hazards model was utilized to explore the prognostic significance of PSA levels in predicting OS adjusting for treatment in all patients and patients who were enrolled on docetaxel trials. Results: IPD from 5,438 patients randomized 1994-2012 from 13 trials were pooled. At 7 months, the proportion of patients who had PSA≤0.1 and PSA ≤0.2 were 18.1% and 26.1%. The median OS in patients who experienced PSA ≤0.1 and PSA≤0.2 and in patients enrolled on docetaxel trials are presented in the table below. The hazard ratios (HR) for death for PSA≤0.1 and PSA≤0.2 vs. those PSA&gt;4 at 4-7 months were 0.26 and 0.27, respectively. In patients enrolled on docetaxel, HRs for death for PSA≤0.1 and PSA≤0.2 vs. those PSA&gt;4 at 7 months were 0.35 and 0.34, respectively. Conclusions: PSA≤0.1 and PSA≤0.2 at 7 months have similar prognostic value of OS in men with mHSPC treated with weak ADT (TS alone) without and with docetaxel. Clinical trial information: NCT00309985 ; NCT00268476 ; NCT00104715 ; NCT00079001 ; NCT00002651 ; NCT00685646 . [Table: see text]
Impact on turnaround times (TAT) among non-squamous non-small cell lung cancer (NSCLC) patients across three time periods with varying biomarker testing techniques.
Authors: Zhen (Jason) Fan, Roxana Tudor, Lisa W Le, Jennifer H. Law, Andrea S. Fung, Shelley Kuang, Nicholas Meti, Kirstin Perdrizet, Laura Ranich, Cuihong Wei, Peter Sabatini, Prodipto Pal, Ming Sound Tsao, Geoffrey Liu, Frances A. Shepherd, Penelope Ann Bradbury, Adrian G. Sacher, Lawson Eng, Michael Cabanero, Natasha B. Leighl
Journal: Journal of Clinical Oncology (2023)

9085 Background: Biomarker testing and identification of actionable genomic alterations (AGAs) in NSCLC patients have led to targeted therapy use and improved outcomes, particularly in advanced stages. We sought to evaluate the impact of different testing paradigms on TAT, particularly with respect to treatment decision and time to initiation of treatment, across three time periods. Methods: A retrospective review of stage III or IV non-squamous NSCLC patients at the Princess Margaret Cancer Centre (Toronto, Canada) was conducted. Both de novo advanced and patients with metastatic progressions are included. Cohort 1 (C1; 01/2015 – 01/2017) underwent reflex EGFR (EntroGen) and ALK (5A4 immunohistochemistry, IHC) single gene testing. Cohort 2 (C2; 02/2017 – 09/2020) underwent reflex next generation sequencing (NGS; Trusight Tumor 15), ALK and ROS1 testing. Cohort 3 (C3; 10/2020 – 01/2022) underwent reflex comprehensive NGS (161 genes, Oncomine OCA v3). Descriptive statistics are presented, including AGAs found and TAT from biopsy to result sign-out, and treatment related TAT. Results: Three cohorts of stage III and IV patients were identified, with C1 having proportionally more females (60%), never smokers (42%) with adenocarcinomas (98%). More patients with AGA were identified using NGS with larger panels (42%, 41%, 57%, respectively across C1 – C3). However, there is a longer median time from first oncology visit to treatment (14, 22, 27 days, respectively across C1-C3), and longer biopsy to treatment TAT trended towards more comprehensive testing (34, 38, 40 days, respectively across C1 - C3) in stage IV patients. Conclusions: As more comprehensive biomarker testing became available, more AGAs are identified with an increase in TAT from biopsy to sign-out and treatment start. Despite our institutional policy of reflex testing, future endeavours will be focus on ways to reduce TAT. [Table: see text]
Impact of pre-treatment anemia on survival in locally advanced head neck squamous cell carcinomas treated with radiation with or without concurrent chemotherapy.
Authors: Minit Jalan Shah, Vijay Maruti Patil, Vanita Noronha, Nandini Sharrel Menon, Ajaykumar Chandrabhan Singh, Kunal Naishadh Jobanputra, Zoya Ravish Peelay, Kumar Prabhash
Journal: Journal of Clinical Oncology (2023)

e18079 Background: Locally advanced head neck squamous cell carcinomas (LAHNSCCs) are treated either with surgery followed by radiation (RT) alone, surgery followed by concurrent chemoradiation (CTRT) or definitive CTRT. Patients receiving RT need to have an optimal hemoglobin (Hb) level, however there is limited data on what is an optimal pre-treatment Hb level required during RT/CTRT in these patients. Hence we performed this analysis. Methods: This data is a pooled analysis of 3 major randomized studies (RCT) performed in the field of chemoradiation over the last decade. These include, a RCT comparing weekly versus (vs) 3 weekly cisplatin in LAHNSCC‘s, weekly cisplatin vs weekly cisplatin plus nimotuzumab in the definitive setting in LAHNSCC‘s and in cisplatin ineligible patients, a comparison of radiation vs docetaxel plus radiation. The baseline demographics, Hb levels, and outcomes were collected and used for analysis. To ensure unanimity, anemia was defined as &lt; 12g/dL in both males and females. Univariate (UVA) and multivariate analysis (MVA) evaluated the factors affecting anemia. The impact of anemia on locoregional control (LRC), disease free survival (DFS) and overall survival (OS) was studied. Kaplan meier analysis was used for estimation of time to event parameters and log rank test was used for comparison. Cox proportional hazards model was used to test the importance of anemia in presence of other important parameters like age, gender, T and N stage, concurrent chemotherapy including its pattern (weekly vs 3 weekly) and site of disease. Results: We studied 1192 patients. Anemia of any grade was seen in 417 patients (35.0%), with the median Hb levels of the entire cohort being 12.8g/dL (IQR 11.6-13.9). Grade 3 or higher anemia (Hb &lt; / = 8g/dL) was seen in only 2 patients (0.2%). Female gender, oral cavity disease, patients with stage IV disease and those receiving adjuvant CTRT significantly impacted anaemia on UVA (p = 0.000 for all). MVA confirmed advancing age (p = 0.001), female gender (p = 0.000), patients with stage III and IV disease (p = 0.009) and those treated with adjuvant CTRT (p = 0.011) to significantly impact anemia. The LRC in patients with or without anaemia was 12.9 months (95%CI 7.8-18.0) and 23.5 months (95%CI 17.8-29.2) respectively (p = 0.000). Similarly the DFS and OS in anemic and non anemic patients were 9.6months (95%CI 6.0-13.2) vs 18.5months (95%CI 12.4-24.7, p = 0.022) and 21.5months (95%CI 16.3-26.8) vs 39.9months (95%CI 31.0-48.9, p = 0.000) respectively. Conclusions: Pre-treatment anemia in LAHNSCC‘s leads to a decrement in treatment outcomes (LRC, DFS and OS) and is an independent prognostic factor.
Development of cervical cancer patient reported clinical outcome assessment scale (CC-PRO137): A dedicated tool for multidimensional evaluation of treatment outcomes.
Authors: Xin Wu, Ling Qiu, Shurong Zhu, Hao Feng, Hui Wang, Yingchun Hou, Tao Zhang, Shen Luo, Hailin Yu, Junda Zhao, Ming Li, Yanan You, Danze Qiao, Yuanyuan Ruan, Yan Du, Hua Jiang
Journal: Journal of Clinical Oncology (2023)

5537 Background: Worldwide, cervical cancer ranks fourth among female malignant tumors in terms of both incidence and mortality. In addition, there is an increasing trend of cervical cancer incidence among younger women. Since the uterus is located at the center of vascular-neural traffic of the pelvic floor, cervical cancer surgery may damage the function of multiple systems such as urinary, digestive, neurological, endocrine, and pelvic floor muscles, and further lead to short- and long-term effects in the psychological domain including sexual status, anxiety, and depression. Therefore, we developed the current scale, Cervical Cancer Patient Reported Clinical Outcome Assessment Scale (CC-PRO137), aimed to construct a functional patient self-report system scale to conveniently and accurately quantify the quality of life of cervical cancer patients from multiple dimensions. Methods: Items included in the scale were proposed by gynecologic oncologist, and were evaluated and modified by experts in various specialties. This scale (CC-PRO137) includes 3 domains and 13 modules, including physiological systems, psychological related symptoms, social life status. A total of 304 participants were tested within 6 and 12 months postoperatively. Subgroup analyses were carried out for different time period, stages, surgical methods and adjuvant treatment plans. Results: The reliability analysis showed that the Cronbach's α in each module of the physiological domain was between 0.602-0.929, the composite reliability was between 0.226-0.946, and the test-retest reliability was between 0.660-0.829; the Cronbach’s α of the psychological domain were between 0.700-0.940, the composite reliability was between 0.584-0.950, and the test-retest reliability was between 0.697-0.807; the Cronbach’s α of the social domain was between 0.836-0.861, the composite reliability was between 0.777-0.886, the test-retest reliability was between 0.732-0.792, and the reliability of each module was optimal. The content validity adopted the expert judgment. Convergent validity (CV) analysis showed that the average variance extraction of each module in the physiological domain was between 0.382-0.706, in the psychological domain was between 0.433-0.801, and in the social domain was 0.440-0.616. The convergent validity of each module was acceptable. Conclusions: Our results showed the effectiveness of CC-PRO137 as a comprehensive assessment tool for cervical cancer patients' quality of life, suggesting that the scale can accurately measure subtle changes postoperatively. CC-PRO137 can be a useful tool to quantitatively assess cervical cancer patients.
Results of SOC-2082 phase 2 study using metronomic gemcitabine, doxorubicin and docetaxel plus nivolumab as second/third-line therapy for advanced sarcoma.
Authors: Nadezhda Omelchenko, Neal Shiv Chawla, Stefan Makrievski, Guilherme Leao De Melo, Chrysler Valencia, Amir Ahari, Ania Moradkhani, Victoria Chua, Doris Quon, Don Arlen Brigham, Sant P. Chawla, Erlinda Maria Gordon
Journal: Journal of Clinical Oncology (2023)

11555 Background: Metronomic dosing of gemcitabine, doxorubicin and docetaxel causes less severe side effects than standard chemotherapy for advanced sarcoma. The addition of nivolumab to this regimen has potential to have synergistic effects and improve treatment outcomes. Methods: Primary objective: To assess progression-free survival (PFS); Secondary objectives: (1) To evaluate best overall response during treatment period confirmed in a 6-week follow-up, (2) PFS rate at 6 and 9 months, (3) Overall survival (OS) rate at 6, 12 months, and (4) Incidence of treatment-related adverse events (TRAEs). Inclusion criteria: Previously treated male and female subjects, ≥ 18 years of age, pathologically confirmed diagnosis of locally advanced, unresectable, or metastatic sarcoma, measurable disease by RECIST v1.1, and acceptable hematologic and organ functions. Exclusion Criteria: History of autoimmune disorder. Treatment schedule: Metronomic doses of gemcitabine (600 mg/m2 max:1000 mg), doxorubicin (18 mg/m2; max: 32 mg), docetaxel (25 mg/m2; max:42 mg) on Day 1 and Day 8, and nivolumab (240 mg) on Day 1 only. Repeat treatment cycles are continued every three weeks if the toxicity grade is ≤1. Results: This report on the modified intent-to-treat population (n=59). This population completed at least one treatment cycle and had a follow-up CT or MRI scan at week 6. Best Overall Response = 8 PR, 44 SD, 7 PD. The disease control rate ( CR+PR+SD) was 88.1%. Median PFS was 5.1 (95% CI: 2.837-7.363) months; 6 month PFS rate 52.5%. Median OS, 15.3 (95% CI: 5.48-25.12) months, with 6-month OS 88%. Safety analysis: Grade 3/4 TRAEs include fatigue (n=18), nausea (n=13), neutropenia (n=10), thrombocytopenia (n=9), anemia (n=9), diarrhea (n=1). There were no unexpected adverse events. Conclusions: Taken together, the data suggests that nivolumab in combination with metronomic doses of gemcitabine, doxorubicin and docetaxel (1) may have synergistic activity, and (2) by indirect comparison, may be as effective as standard first line therapy for advanced sarcoma with manageable toxicity. Clinical trial information: NCT04535713 .
Response to immune checkpoint inhibitor (ICI) rechallenge in patients with metastatic renal cell carcinoma who progressed on prior ICI: A systematic review and meta-analysis.
Authors: Garima Gupta, Donglin Yan, Zin Myint
Journal: Journal of Clinical Oncology (2023)

4547 Background: Several immune checkpoint inhibitor (ICI)-based combination regimens are standard-of-care for first-line treatment of metastatic renal cell carcinoma (mRCC). These include dual ICI and ICI-tyrosine kinase inhibitor (TKI) combinations. While single-agent ICI is recommended as subsequent-line therapy for ICI-naïve patients, there is limited knowledge regarding efficacy of rechallenging with a different ICI or using different ICI combinations in patients who have progressed on prior ICI therapy. This is a clinically critical question as most mRCC patients would have already received ICI therapy at progression. The aim of this study is to address the above by performing a systematic review and meta-analysis. Methods: PubMed, Cochrane Library and Web of Science were systematically searched to identify studies of later-line ICI rechallenge after progression on any previous ICI in mRCC patients from database inception to December 31 st , 2022. Patients who had progressed on prior ICI and rechallenged with ICI as single agent/dual/TKI combination as any subsequent line of therapy in both retrospective and prospective studies were included. Exclusion criteria were phase I or any phase studies combining ICI with unapproved drugs, case reports and case series. We calculated the pooled objective response rate (ORR) and disease control rate (DCR) using mixed effects model treating individual studies as a random effect. We further stratified studies into prospective and retrospective and performed subgroup analyses. Results: A total of 11 studies, 6 prospective and 5 retrospective with a total of 603 patients were initially identified. Out of the 6 prospective studies, 3 had an adaptive design of using salvage ipilimumab/nivolumab in patients who had either progressed or had stable disease as the best overall response on nivolumab monotherapy. These studies were excluded as they did not meet our inclusion criteria. A total of 8 studies with 400 patients were included in the final analysis. The ORR was 28% (95% CI, 0.27-0.36) and the DCR was 70% (95% CI, 0.47-0.85) with no significant differences between prospective and retrospective studies. Our ORR is higher than an earlier meta-analysis reporting an ORR of 14% with salvage ipilimumab/nivolumab after previous treatment with ICI. Conclusions: This meta-analysis demonstrates a modest ORR and an impressive DCR. Therefore, it provides strong clinical rationale to consider rechallenging with ICI-based therapy for later-line treatment of mRCC patients who have progressed on prior ICI. [Table: see text]
Clinical outcomes in patients with post-chemotherapy residual non-retroperitoneal (RP) disease in non-seminomatous germ-cell tumors (NSGCT).
Authors: Jennifer King, Ryan Ashkar, Kenneth Kesler, Sandra K. Althouse, Nasser H. Hanna, Lawrence H. Einhorn, Nabil Adra
Journal: Journal of Clinical Oncology (2023)

e17027 Background: In patients (pts) with metastatic NSGCT, the presence of teratoma in the primary tumor specimen or in the post-chemo RP lymph node dissection (RPLND) has previously been shown to have no impact on prognosis. We report clinical outcomes of pts based on pathology in primary tumor and from post-chemotherapy non-RP disease surgical resection. Methods: The prospectively maintained Indiana University testicular cancer database was queried for pts with metastatic NSGCT treated between 1990-2021 who completed first-line chemotherapy and had residual extra-RP disease in the absence of residual RP disease. Pts who had post-chemo non-RP surgical resection were included. Kaplan-meier methods were used to analyze progression-free survival (PFS) and overall survival (OS). Results: 131 pts met eligibility. Median age at diagnosis was 28.6 (range, 16.2-51.5). Primary site was testis in 130 pts (99%). Primary tumor predominant histology was embryonal (34.4%), mixed (26%), choriocarcinoma (14.5%), teratoma (11.5%), yolk sac (10.7%), seminoma (1.5%). Metastatic sites at diagnosis were lung (27.5%), brain (19.8%), RP (14.5%), liver (8.4%), mediastinal LN (7.6%), bone (7.6%). All pts with RP mets at diagnosis had normalization of RP nodes after chemo. All pts had surgical resection of non-RP disease. None had RPLND. IGCCCG risk was good in 56, intermediate in 23, and poor in 52 pts. Median pre-chemo AFP was 66.7 (0.9-467,000). hCG was 692 (0.5-500,000). First-line chemo was BEPX4 in 68, BEPX3 in 29, EPX4 in 10, VIPX4 in 8, and other in 16 pts. 76 pts (58%) had teratoma in the primary tumor. Median follow-up was 3.16yrs. 2-yr PFS for pts with teratoma in primary was 59% (95% CI 45-71) vs. 54% for pts without (95% CI 38-67); p = 0.42. 2-yr OS for pts with teratoma in primary was 85% (95% CI 73-92) vs. 70% for pts without (95% CI 54-81); p = 0.18. 2-yr PFS and OS based on pathology and location of non-RP site are listed in Table 1. Conclusions: The presence of teratoma in primary tumor and post-chemotherapy non-RP resections is not associated with worse PFS or OS in pts with metastatic NSGCT. [Table: see text]
NEOSPACE trial: Neoadjuvant pembrolizumab-gemcitabine-cisplatin followed by concurrent pembrolizumab-chemoradiation and maintenance pembrolizumab for stage IVA nasopharyngeal cancer (NPC).
Authors: Edwin P Hui, Brigette Ma, Darren Wan-Teck Lim, WK Jacky Lam, Yoke Lim Soong, Leung Li, Kenneth C.W. Wong, Daisy Lam, Florence Mok, Macy Tong, Darren MC Poon, Chi Hang Wong, Frankie Mo, Ann Dorothy King, Kwok-Wai Lo, Jason Y.K. Chan, KC Allen Chan, Anthony T. C. Chan
Journal: Journal of Clinical Oncology (2023)

6010 Background: Stage IVA NPC had the worst prognosis despite the current standard of neoadjuvant chemotherapy and concurrent chemoradiation (CRT). There is no safety and efficacy data combining immune checkpoint inhibitor (ICI) and CRT in NPC. Methods: We conducted an open label, single arm, multi-site, phase 2 clinical trial in AJCC 8th Edition Stage IVA (T4 and/or N3, M0) WHO type 2/3 Epstein Barr virus (EBV) +ve NPC (Clinical trial register NCT03734809). The experimental treatment consisted of neoadjuvant pembrolizumab (200 mg D1), gemcitabine (1000 mg/m2 D1+8) and cisplatin (80 mg/m2 D1) q3w x2 followed by concurrent pembrolizumab (200 mg x3 week 1, 4 and 7) and cisplatin (40 mg/m2 weekly x7) during intensity-modulated radiation (IMRT), and maintenance pembrolizumab 200 mg q3w x12 from 4 weeks post-RT. By Fleming one-stage design (type I error 0.05, power 0.80, 10% drop out), planned sample size is 46. Primary endpoint is 2-year (yr) progression free survival (PFS). Secondary endpoints include safety and tolerability. Plasma EBV DNA (pEBV DNA) was monitored. Results: Accrual was completed with 46 subjects recruited at two study sites from May 2019 to June 2022 in Hong Kong (n=31) and Singapore (n=15). This protocol specified analysis included 37 subjects with &gt;12 months post-treatment follow up (median 26.8 months, 95% CI 21.3-32.9). Patient demographics: mean age 52 (range 27 - 84); M:F 31:6; ECOG 0=23, 1=14; stages: T4N1-2 (16), T1-3N3 (18), T4N3 (3). Overall compliance rate: neoadjuvant cisplatin 98.6%, gemcitabine 97.7%, concurrent cisplatin 73.7%, pembrolizumab 100% (neoadjuvant), 77.5% (concurrent), 77% (maintenance), IMRT 99.7% (69.96 Gy). Treatment related adverse events (≥ grade 3, &gt;10%): dysphagia (32.4%), mucositis (29.7%), neutropenia (29.7%), radiation dermatitis (24.3%), anemia (18.9%), hyponatremia (13.5%), thrombocytopenia (10.8%). No ≥ grade 4 mucositis/dermatitis. The 2-yr PFS was 69.6% (95% CI 53.8 - 88.5%). At the end of neoadjuvant, CRT and maintenance phases, molecular remission (pEBV DNA = 0) was achieved in 24.3%, 70.3% and 70.3% of patients respectively, which strongly correlated with PFS (p=0.0253, 0.0007 and &lt;0.0001 respectively, Table). Conclusions: Pembrolizumab incorporated into neoadjuvant, CRT and maintenance protocol is safe with promising results. This strategy of combining ICI with neoadjuvant chemotherapy and CRT is being tested in several ongoing phase 3 trials in advanced NPC. Clinical trial information: NCT03734809 . [Table: see text]